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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
TAK-715 is a novel, potent and selective p38 MAPK (p38 mitogen-activated protein) inhibitor with potential anti-inflammatory activity. It has an IC50 of 7.1 nM, is 28-fold more selective for p38 than p38, and exhibits little to no inhibition of JNK1, ERK1, IKK, MEKK1, or TAK1. It also shows little to no inhibition of p38γ/δ, and inhibits p38α only. For the treatment of Rheumatoid arthritis-RA, TAK-715 is currently being studied in clinical trials.
Targets |
p38α (IC50 = 7.1 nM); p38β (IC50 = 200 nM); p38δ (IC50 >10 μM); p38γ (IC50 >10 μM); CK1δ; CK1ε
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ln Vitro |
TAK 715 has an IC50 of 48 nM and inhibits LPS-stimulated TNF-alpha release from THP-1. [1] Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells are inhibited by TAK 715 (10 μM).[2] The main-chain carbonyl of Met109 of p38 alpha is hydrogen bonded to the amide NH of TAK 715. TAK 715 occupies the hydrophobic back pocket, the adenine region, the front pocket of p38, as well as the majority of the length of the Gly-rich loop, and binds relatively high in the ATP pocket.[3]
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ln Vivo |
TAK 715 (10 mg/kg, po) reduces the amount of TNF-alpha produced by LPS in mice by 87.6%. TAK 715 has a modest bioavailability in mice of 18.4% and a marginally better bioavailability in rats of 21.1%. TAK 715 has a modest bioavailability in mice of 18.4% and a marginally better bioavailability in rats of 21.1%. Rats treated with TAK 715 have a Cmax of 0.19 μg/mL and an AUC(0-24 hours) of 1.16 μg/h/mL. In a rat adjuvant-induced arthritis (AA) model, TAK 715 (30 mg/kg, po) significantly lowers the secondary paw volume with 25% inhibition. [1]
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Enzyme Assay |
TAK-715 is a p38α MAPK inhibitor with an IC50 of 7.1 nM that is 28-fold more selective for p38α over p38β, with no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1.
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Cell Assay |
TAK 715 has an IC50 of 48 nM and inhibits LPS-stimulated TNF-alpha release from THP-1. In U2OS-EFC cells, TAK 715 (10 μM) prevents Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift. The main-chain carbonyl of Met109 of p38 alpha is hydrogen bonded to the amide NH of TAK 715. TAK 715 occupies the hydrophobic back pocket, the adenine region, the front pocket of p38, as well as the majority of the length of the Gly-rich loop, and binds relatively high in the ATP pocket.
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Animal Protocol |
Adjuvant-induced arthritis (AA) rat model
30 mg/kg Orally |
References |
Molecular Formula |
C24H21N3OS
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Molecular Weight |
399.51
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Exact Mass |
399.14
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Elemental Analysis |
C, 72.15; H, 5.30; N, 10.52; O, 4.00; S, 8.03
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CAS # |
303162-79-0
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Related CAS # |
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Appearance |
Light to dark yellow solid powder
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SMILES |
CCC1=NC(=C(S1)C2=CC(=NC=C2)NC(=O)C3=CC=CC=C3)C4=CC=CC(=C4)C
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InChi Key |
HEKAIDKUDLCBRU-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H21N3OS/c1-3-21-27-22(18-11-7-8-16(2)14-18)23(29-21)19-12-13-25-20(15-19)26-24(28)17-9-5-4-6-10-17/h4-15H,3H2,1-2H3,(H,25,26,28)
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Chemical Name |
N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]pyridin-2-yl]benzamide
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Synonyms |
TAK 715; TAK715; TAK-715
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5031 mL | 12.5153 mL | 25.0307 mL | |
5 mM | 0.5006 mL | 2.5031 mL | 5.0061 mL | |
10 mM | 0.2503 mL | 1.2515 mL | 2.5031 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00760864 | Completed | Drug: TAK-715 and methotrexate Drug: Methotrexate |
Arthritis, Rheumatoid | Takeda | August 2004 | Phase 2 |